Ion channels are channels extending through the cell membrane, and are classified broadly into two types: ligand-dependent channels and potential-dependent channels. In recent years, as a type of mechanism of neuropathic pains, a potential-dependent sodium channel and a potential-dependent calcium channel have been found as a target. As drugs targeting a potential-dependent sodium channel, for example, lidocaine, carbamazepine, lamotrigine, mexiletine and the like are known. As drugs targeting a potential-dependent calcium channel, for example, gabapentin pregabalin, ziconotide and the like are known.
The neuropathic pain is refractory, and has the problem of inadequate response to existing analgesic drugs. The efficacy of even an established drug therapy is difficult to predict accurately, and other drugs must often be used in combination. In “Guidelines for the Pharmacologic Management of Neuropathic Pain” from Japan Society of Pain Clinicians, high-potential-activated calcium channel inhibitors are listed as a primary choice, but in many cases, an adequate therapeutic effect is not obtained. These inhibitors have a problem of causing side effects such as lightheadedness.
Potential-dependent calcium channels are classified into two types: high-potential-activated types and low-potential-activated types based on a difference in activation and deactivation potentials. L-type, N-type, P/Q-type and R-type calcium channels are activated by large depolarization, and therefore classified as high-potential-activated calcium channels. On the other hand, T-type calcium channels are activated by small depolarization, and therefore classified as low-potential-activated calcium channels.
Recently, T-type calcium channels have been reported to be involved in onset and development of a neuropathic pain, and potential of T-type calcium channel inhibitors as therapeutic agents for the pain has been suggested. Examples of the T-type calcium channel inhibitor include mibefradil (see, for example, Todorovic, Neuron, 2001, 31 (1), p. 75-85 (Non-Patent Document 1)), ethosuximide, and (1S,2S)-2-[2-[3-(1H-benzimidazol-2-yl)propyl]methyamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl-cyclopropane carboxylate hydrochloride (NNC55-0396) (see, for example, Huang, J Pharmacol Exp Ther., 309(1), p. 193-199 (Non-Patent Document 2)). Thus, some compounds have already been found as T-type calcium channel inhibitors, but further studies on new T-type calcium channel inhibitors are required in view of side effects etc.
Flavanone compounds having a flavanone backbone are compounds contained in natural extracts etc. These flavanone compounds have been found to have various drug efficacies. For example, it has been found that sophoraflavanone G which is a type of flavanone compound can be used as an antibacterial agent having an inhibitory action on proliferation of Propionibacterium acnes and Pityrosporum ovale (Japanese Patent No. 3327699 (Patent Document 1)). For example, Japanese Patent No. 4393062 (Patent Document 2) discloses that extracts from Sophora, which contain a flavone selected from the group consisting of 8-prenylnaringenin, kushenol X, 8-prenylkaempferol, leachianone G and kushenol E, an alkaloid, an isoflavone, a chalcone and a pterocarpan are capable of preventing and treating disease conditions caused by abnormal metabolism of estrogen. On the other hand, it is not disclosed that the flavanone compound has a T-type calcium channel inhibitory action.